Bioactive peptides are known to exhibit various pharmacological actions in a living body, and are intended to apply for pharmaceuticals. However, these bioactive peptides must be administered frequently since they have generally short half-life in a living body, therefore physical burden of patients due to the frequent injections can be considerable. For example, growth hormone (hereinafter referred to as GH), a representative hormone which is originally produced and secreted in the anterior pituitary gland, is a bioactive peptide having widely diverse physiological activities such as growth stimulation in the body, metabolism of glucose and lipids, anabolism of protein, and cell proliferation and differentiation. The GH has been recently produced on a large scale with Escherichia coli using genetic recombination technology, and put to clinical use worldwidely as medicine. However, GH must be frequently administered in order to maintain an effective blood level because of its short biological half-life. Especially, in the case of GH− deficient short stature, practically GH is administered daily by subcutaneous injection to infants or young patients over a long period of time ranging from a few months to 10 years or more.
In order to deal with the problems inherent in bioactive peptide medicine, various drug delivery systems have been studied. For example, a sustained-release agent that provides sustained-release of a bioactive peptide for a long period is exemplified. JP 8-217691 A (WO96/07399) discloses a production method for a sustained-release preparation containing a water-insoluble or poorly water-soluble multivalent metal salt and a biodegradable polymer, wherein the metal salt is formed from a water-soluble peptide bioactive substance and an aqueous solution of zinc chloride and the like. Furthermore, JP 11-322631 A discloses a production method for a sustained-release preparation comprising adding a water-miscible organic solvent and/or a volatile salt to an aqueous solution of a bioactive peptide, followed by lyophilizing to obtain bioactive peptide powder, dispersing the powder in a solution of a biodegradable polymer in an organic solvent, and removing the organic solvent. Moreover, in a production method for a sustained-release microcapsule containing a bioactive substance and a biodegradable polymer, JP 9-132524 A discloses a production method for providing a sustained-release preparation which contains very little residual organic solvent and has very superior clinical characteristics as a medicine, comprising forming microcapsules and heat-drying the microcapsules at the temperature of not less than the glass transition temperature of the biodegradable polymer for about 24 to 120 hr.